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Skull base osteomyelitis


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Skull base osteomyelitis

  1. 1. SKULL BASE OSTEOMYELITIS: Fungal vsBacterial infection ( C.C Blyth et al, ClinMicrobiol Infect 2011;17:306-311 DR KAMLESH K DUBEY Deptt. Of Otorhinolaryngology AIIMS, New Delhi
  2. 2. INTRODUCTION First described in 1959 by Meltzer and Kelemen Skull-base osteomyelitis (SBO) is an uncommon condition Associated with significant morbidity and mortality Described most often as a complication of malignant otitis externa secondary to Pseudomonas aeruginosa infection May also occur in the absence of malignant otitis externa and with pathogens other than Pseudomonas aeruginosa, including fungi. Fungal SBO : Aspergillus, Scedosporium spp.
  3. 3. INTRODUCTION RISK FACTORS:a) Increasing ageb) Diabetes mellitusc) Microvascular diseased) Immunodeficiencies: primary / acquired Fungal SBO has also occurred in the absence of these traditional risk factors
  4. 4. INTRODUCTION ESSENTIALS OF MANAGEMENT OF SBO:I. Early diagnosisII. Identification of the causative pathogensIII. Prompt initiation of appropriate antimicrobial or surgical therapiesIV. Continuation of therapy for an adequate period
  5. 5. AIMS & OBJECTIVES Compare the epidemiology and clinical characteristics of bacterial and fungal SBO Aiming to identify unique risk factors and clinical associations
  6. 6. Material and Methods Study design: retrospective study over 18 years(1990-2007). Cases identified following interrogation of medical records using International Statistical Classification of Diseases and related Health Problems definitions Otorhinolaryngology, Histopathology and Microbiology data bases were also queried for cases of SBO. Approval for the study was obtained from Sydney West Area Health Service Human Research Ethics Committee
  7. 7. Material & Methods For each patient clinical information was recorded on a standardized form and included:a) Patient demographicsb) Comorbidities & predisposing factors within 90 daysc) Likely source of infection : ear, sinuses, otherd) Clinical featurese) Results of microbiological and histopathological investigationsf) Treatmentg) Hospital length of stayh) Clinical outcomes
  8. 8. Materials & MethodsResults of computed tomography(CT), magnetic resonanceimaging (MRI) and bone scan Technitium-99m/gallium citrate(Ga)-67 were assessed by radiologist who was blinded to otherresults.
  9. 9. Materials & Methods Definitions :A. Definite : skull base infection in patients with localizingsymptoms/signs at presentation who had:i. Radiological or scintigraphic features indicative of bone erosion and/or infection.ii. Isolation and/or visualization of pathogen from affected bone(s) and surrounding tissue.
  10. 10. Materials & MethodsProbable SBO:Infection in patients with localizing symptoms/signs withevidence of SBO on imaging studies, but from whom apathogen was recovered from clinical specimens other thanbone or tissue (e.g. ear swabs) or in whom a definitiveresponse to antimicrobial therapy was evident.Primary source of pathogen:Assigned according to patient clinical features in context ofaccompanying microbiological and radiological results.
  11. 11. Materials & MethodsStatistical analysis :I. Clinical data analyzed using SPSS, version 15.0.0 ( SPSS Inc., Chicago, IL USA).II. Variables associated with SBO caused by bacteria were compared with those associated with fungal SBOIII. Analyses were also performed to examine risk factors, presenting symptoms, causative pathogen, and treatments administered associated with survival at 6 months.IV. Univariate analyses were performed using a Student’s t-test (for continuous variables) or Chi-square or Fisher’s exact tests( for categorical variables)V. p<0.05 was considered statistically significant
  12. 12. RESULTS DEMOGRAPY:i. -From over 500 patients identified through search, 21 patients met the case definition of SBO.ii. 15 had proven SBO and six had probable infection.iii. Mean patient age was 58 years (range 26-80 years)iv. 66.7% -male
  13. 13. RESULTSPredisposing factors:i. Diabetes mellitus was most frequent predisposing factor--- -12 patients ; 57%ii. Chronic otitis externa 33%iii. chronic sinusitis 29%iv. Immunosuppression 10%v. Trauma or surgery 30%
  14. 14. RESULTS Median time to presentation:i. Bacterial - 26.3 weeks (4.2-28.5)ii. Fungal - 8.1 weeks (0.6-15.5)
  15. 15. CLINICAL BACTERIAL FUNGAL SIGNIFICANCEFEATURESFEVER 3 (30.0%) 6 (54.5%) NSHEADACHE 4 (40.0%) 8 (72.7%) NS RESULTSDEAFNESS 7 (70.0%) 2 (18.2%) p 0.03EAR PAIN 8 ((80.0%) 2 (18.2%) p<0.009EAR DISCHARGE 8 (80.0%) 1 (9.1%) p<0.002SINONASAL PAIN 1 (10.0%) 8 (72.7%) p<0.008FACIAL OR 1 (10.0%) 7 (63.6%) P 0.024PERIORBITALSWELLINGNASAL 3 (30.0%) 9 (81.8%) p 0.03STUFFINES ORDISCHARGECRANIAL NERVE 5 (50.0%) 5 (45.5%) NSINVOLVEMENTEYE/ORBIT 0 2 (18%) -INFECTION
  19. 19. DISCUSSION SBO is uncommon infection Complication of uncontrolled otogenic, odontogenic or sinus infection Large adequately powered epidemiological studies have not been published Present study, using strict case definitions for SBO, reveals that fungi accounted for a significant proportion : approx. 50% of SBO Significant morbidity of SBO in the present study is consistent with previous reports
  20. 20. DISCUSSION Almost half (48%) of patients had persistent cranial nerve abnormalities, other reports 21-43%. Extension into brain uncommon. Cerebral involvement has been associated with high mortality in reported cases despite surgical intervention. As reported in other studies, diabetes mellitus and chronic ear disease. Confirmation of underlying chronic sinusitis as a risk factor for SBO is required.
  21. 21. DISCUSSION Otogenic Pseudomonas aeruginosa infection accounted for 50% of bacterial SBO. SBO complicating malignant otitis externa is almost uniformly caused by this bacterium Other bacteria and fungi are also important causes of SBO Fungal SBO is increasingly reported in literature Apparent rise reflect apparent rise in use of immunosuppressive therapy Importantly however fungal SBO may also occur in immunocompetent individuals
  22. 22. DISCUSSION Most cases of fungal SBO has been due to Aspergillus or Scedosporium spp., reportedly arising from contiguous spread of ear infection Authors observed that fungal SBO occurred primarily as a result :i. Underlying sinus infectionii. Zygomycetes were most frequent pathogen Reasons fro relative prevalence Zygomycetes not readily apparent but are of interest Zygomycetes are well known pathogens of invasive fungal sinus
  23. 23. DISCUSSION Although not statistically significant, majority >70% fungal SBO patients had diabetes (known risk factor for zygomycetes) There may be differences in clinical risk factors and associations for bacterial and fungal SBO
  24. 24. DISCUSSIONFungal SBO features: More likely to have underlying chronic sinus disease Symptoms attributable to invasive sinus infectiona. Sino-facial painb. Periorbital swellingc. Nasal stuffiness/discharge Absence of purulent ear discharge was a sensitive (91%) predicator of underlying fungal SBO Clinical failure with antibacterial therapy should also promt similar considerations
  25. 25. DISCUSSIONTREATMENT OPTIONS: Antimicrobial therapyi. Because P. aeruginosa infection predominates in most case series of bacterial SBOii. Initiation of antibiotics with activity against P. aeruginosa is appropriate pending microbiological diagnosisiii. Because zygomycetes were responsible for >50% of fungal SBO use of regimens including high-dose amphotericin B formulations is advised pending definitive diagnosis
  26. 26. DISCUSSIONTREATMENT OPTIONS:ROLE OF SURGERY:I. Likely influenced by pathogenII. Early surgery is associated with improved survival in patients with improved survival in patients with zygomycosisIII. Aggressive surgical debridement is recommended in fungal SBOIV. Probably unnecessary in patients with bacterial SBO
  27. 27. Skull base osteomyelitis: diagnostic andtherapeutic challenges in atypical presentation( A.Singh et al. Otolaryngology head and neck surgeryvolume 133, Issue 1, july 2005;121-125 Objectives :To document diagnostic and management difficulties inmasked skull base osteomyelitis secondary to malignant otitisexterna, emphasis on establishing diagnostic criteria inrecurrence. Study design:Retrospective analysis of 3 cases of inadequately treatedmalignant otitis externa in elderly diabetic individuals leading torecurrence and atypical manifestations of skull baseosteomyelitis on contralateral side with or without multiplecranial nerve involvement.
  28. 28.  Result :i. Two of 3 cases died despite aggressive treatmentii. One case treated successfully with combination of antipseudomonal microbial drugs for 8-12 weeks and hyperbaric oxygen therapyiii. Major complications observed were:a. thrombosis of lateral sinus and IJV thrombosisb. Meningitisc. Ophthalmoplegiad. Blindnesse. Cervical spine erosionf. Paralysis of all cranial nerve except 1st C.N
  29. 29. Management of osteomyelitis of anterior skullbase and craniovertebral junction(Yadranko Ducic. Otolaryngology Head Neck Surg2003;128:39-42) Objectives :To determine patient demographics, identify predisposingfactors and determine efficacy of treatment for nonotologicosteomyelitis of skull base and craniovertebral junction Study design:All patients with biopsy proven diagnosis of osteomyelitis ofskull base treated by author from 1997 through 2001 wereretrospectively evaluated
  30. 30.  Results :i. Six patients were identified on reviewii. Average age of presentation was 56.7 years (38-70 yrs.)iii. All except one had immunocompromising condition (DM, HIV, Steroid use)iv. Most presented with neurologic deficits associated with a destructive lesion of osseous skull basev. Aggressive debridement of involved bone enabled through use of broad field standard skull base approaches were associated with clinical resolution in each casevi. Systemic antibacterial/antifungal therapy and medical optimization remain important adjuncts in treatment of this group of patientsvii. In the absence of any persistent neurologic deficit and in the presence of a normal ESR, reasonable to discontinue systemic therapy after 6 weeksviii. Persistent elevation of ESR or a return of symptoms would mandate repeat imaging, including gallium scanning
  31. 31.  Conclusion:i. Nonotologic osteomyelitis of skull base and craniovertebral junction is a locally aggressive disorder causing lytic destruction of skull base bone often with underlying dural enhancementii. Systemic immunocompromise i.e. is usually notediii. Aggressive surgical debridement of all affected bone achieved through broad field exposure afforded by modern skull base approachesiv. Culture guided antifungal or antibiotic therapy
  32. 32. Cranial nerve involvement in malignant externalotitis: implication for clinical outcome(Mani N Laryngoscope.2007May;117(5):907-10) Objective :To determine whether cranial nerve involvement in malignantexternal otitis affects or predicts clinical outcome in terms ofmorbidity and mortalityMethods:Diagnosis of malignant otitis externa established in 23 patientsbased on inclusive criteria:i. Severe painii. Otitis externa refractory to conventional treatmentsiii. Diabetes mellitusiv. Pseudomonas aeruginosa infection detection
  33. 33.  Data analysis:Retrospective analysis of hospital records
  34. 34.  Results :i. Ten of 23(43.5%) patients showed cranial nerve involvementii. Cranial nerve affected were:a. facial nerve (6/10)b. Lower cranial nerves (combination of IX,X,XI,XII)c. Extended nerve palsy(VI,VII,IX,X,XI)(1/10)d. 13/23(56.5%) patients displayed no cranial nerve involvemente. All patients treated with long term, high dose antibiotic treatment dependent on the microbiological findings
  35. 35.  Conclusions:i. All patients with lower cranial nerve palsy recovered normal functionii. Facial nerve palsy was significantly less likely to improve by medical treatmentiii. Cranial nerve involvement did not affect patient survival rate under an optimized medical treatment
  36. 36. Otogenic cranial base osteomyelitis: a proposedprognosis-based system for disease classification(Lee S. Otol Neurotol.2008 Aug;29(5):666-72 Objectives:To review presentation , microbiology, and long term results of treating otogenic cranialbase osteomyelitis to develop a prognosis based classification system Patients & Method:i. 38 patients with otogenic cranial base osteomyelitis treated between 1989-2002ii. Patient demographics, presentation, pathogens, details of therapy, and disease specific survival were recordediii. Patients stratified using Tc-99 single photon emission computerized tomography(SPECT) at presentation in to 4 grades: grade I- mild uptake, grade II- focal mastoid/temporal bone uptake not reaching midline grade III- petrous temporal bone uptake reaching midline grade IV- uptake crossing midline, involving contralateral temporal bone
  37. 37.  Results :i. 27/38 menii. Average age at presentation 65+/- 16 yrsiii. Mean adjusted charlson comorbidity score was 5 & 63% of patients were diabeticiv. Most common presenting symptoms: pain, otorrheav. 8 patients had cranial nerve neuropathyvi. Antibiotics were administered for 161 days, 6 patients had concomitant surgeryvii. Avg. f/u was 33 monthsviii. 3 year disease-specific survival was 76%
  38. 38. Results :-Univariate predictors of survival were:i. SPECT gradeii. Fungal/mixed infectionsiii. Charlson scoreiv. Immune compromisev. Cranial nerve neuropathy-only independent predictor of survival on multivariate Cox regression wasSPECT stage at presentationConclusion :Cranial base osteomyelitis is associated with significantmorbidity, mortality and requires prolonged treatmentLong term outcome can be predicted from initial SPECT scan
  39. 39. Outcomes of malignant external otitis: survival vsmortality(Chen CN. Acta Otolaryngol.2010;130(1):89-94) Objectives :To analyze factors that affect survival of patients with MEO intodays era of advanced antibiotics Patients & Methods:Patients with a diagnosis of MEO from 1993-2005 were collected Results:i. 26 patients with mean age 63.7±10.2 years were includedii. All had history of diabetes mellitusiii. Most frequent pathogens: Pseudomonas aeruginosa 26.9% Klebsiella pneumoniae 19.2% Fungus 15.4%
  40. 40.  Results cranial nerves were involved in 11 patientsFacial nerve was most frequently(38.46%) involvedComplications such as intracranial involvement were notedMastoidectomy performed in 12 patientsTotal of five patients died Conclusion:i. Mortality was not related to age , sex , degree of glucose intolerance, duration of diabetes mellitus, microorganism, comorbid disease or involvement of a single cranial nerveii. Intracranial involvement and multiple cranial nerves involvement were correlated with mortality
  41. 41. Malignant otitis externa(Matthew J. Carfrae. Otolaryngol Clin NAm.41;(2008):537-549 Results :i. With current cranial nerve involvement does not preclude cureii. Patient may have incomplete recover of facial nerve functioniii. Lower cranial nerves exhibited good recovery Conclusion :Poor prognostic factor includei. Fungal infectionii. MRI finding of middle cranial fossa and foramen magnum dural inhancement
  42. 42. Final Discussion Skull base osteomyelitis: infection spread to skull base beyond external auditory canal Diabetes mellitus remains most important associated condition:Because of associated:i. Endarteritisii. Microangiopathyiii. Small vessel obliteration Pathophysiology: Pseudomonas aeruginosa has ability to invadevessel walls and cause a vasculitis with thrombosis andcoagulation necrosis of surrounding tissueCellulitis->chondritis->osteitis->osteomyelitis
  43. 43.  Pathophysiology:i. Infection from EAC spreads to skull base through fissures of santorini, small perforations in cartilaginous portion of EAC along floor of canalii. Compact bone of skull base becomes replaced with granulation tissue leading to bone destructioniii. Progressive spread of infection to skull base foramina causes cranial neuropathiesiv. Most common nerve involved Facial nerve because of proximity of stylomastoid foramen to EACv. Nerves of jugular foramen next to get affectedvi. More medial spread to petrous apex can affect abducens and trigeminal nerves & further medial optic nervevii. Spread of infection to sigmoid sinus can lead to septic thrombosis of sigmoid and internal jugular veinviii. Intracranial complication: meningitis , cerebral abscess
  44. 44.  Levenson’s criteria:i. Refractory otitis externaii. Severe nocturnal otalgiaiii. Purulent otorrheaiv. Granulation tissue in external canalv. Growth of pseudomonas aeruginosa from EACvi. Presence of diabetes and other immunocompromised statevii. Positive bone scan
  45. 45. Cohen D, Fredman P. The diagnostic criteria ofmalignant external otitis. J Laryngol Otol1987;101:216-21A. Obligatory :i. Painii. Edemaiii. Exudatesiv. Granulationsv. Microabscess(when operated)vi. Positive bone scanvii. Failure of local treatment after >1week treatmentviii. Possibly pseudomonas in culture
  46. 46.  Cohen’s diagnostic criteria:B. Occasional :i. Diabetes mellitusii. Cranial nerve involvementiii. Positive radiographiv. Debilitating conditionv. Old age
  47. 47. Staging system Corey (1985)i. Stage I: infectionii. Stage II: involving cranial nervesiii. Stage III: intradural spread Benecke (1989):i. Stage I: Necrotizing otitis externa: soft tissue infectionii. Stage II: limited skull base osteomyelitisiii. Stage III: extensive skull base osteomyelitis with involvement of occipital bones, facial bones, and contralateral extension
  48. 48. Staging System Levenson’s Davis’s staging system(1992) Dr A. Thakar, D. A. Tandon, S. Bahadur, S. K. Kacker (1996)
  49. 49.  Scott-Brown’s Otorhinolaryngology Head n Neck Surgery staging (by combining three staging system published between 1985-1991)Stage 1: clinical evidence of malignant otitis externa with soft tissue infection beyond external auditory meatus, but negative 99mTc bone scanStage 2: soft tissue infection beyond external auditory meatus with positive 99mTc bone scanStage 3: as stage 2 but with cranial neuropathy 3a: single 3b: multipleStage 4: as stage 2/3 with intracranial complications (meningitis, empyema, sinus thrombosis, brain abscess)
  50. 50.  Microbiology :A. Bacterial : P. aeruginosa, S. aureus, S. epidermis, P. mirabilis, K. oxytoca, P. cepaciaFeatures of pseudomonas: gram negative obligate aerobe contain mucoid surface layer protecting against phagocytosisProduce: lytic enzymes- collagenase, elastase, also endotoxinB. Fungal :Aspergillus fumigatus, A. flavus, A. niger, Scedosporiumapiospermum,
  51. 51. ETIOLG AGE DIABET IMMUN GRANU ME/MA HISTOLY ES OSUPP LATION STPID OGY RESSIO TISSUE INVOLV N EMENTBACTE older common common Gm-rodRIA + -(pseudomona)FUNGA younger Less More - + BranchinL common common g(aspergil septatedlus) hyphae, calcium oxalate crystal
  52. 52. Diagnosis :A. HistoryB. Clinical examinationC. Laboratory studies: CRP , ESRD. Imaging studies
  53. 53.  Clinical examination:i. Tympanic membrane usually normalii. EAC skin soggy , edematousiii. Scanty and foul smelling dischargeiv. Foul smelling discharge the onset of osteomyelitisv. Patients usually dose not have fever or other constitutional symptomsvi. Cranial nerve palsies
  54. 54.  Imaging :CTMRINUCLEAR IMAGING
  55. 55.  CT:i. Sensitive to bone erosion and decreased skull base densityii. Sensitive in diagnosing: abscess formation, involvement ofmastoid, temporomandibular joint, infratemporal fossa, petrousapex, carotid canaliii. Demineralization of skull base of ≥30% is identifiable on CTscaniv. These changes persist despite resolution of disease, thereforepoor choice for measuring treatment responsev. Inadequate for showing intracranial extension and bone marrowinvolvement
  56. 56.  MRI:i. Shows changes in soft tissue (particularly dural enhancement and involvement of medullary spaces)ii. Persistence of these changes despite resolution makes MRI poor study for determining disease resolution
  57. 57.  Nuclear imaging:Technetium Tc99m methylene diphosphonate (MDP)scintigraphy:i.Concentrate in areas with osteoblastic activityii. Allows earlier diagnosis of osteomyelitis than CTiii.Not specific for infection
  58. 58.  Gallium Ga67 citrate :Concentrates in areas of active inflammation through attachingto lactoferrin (present in large quantities in leukocytes-Binding to transferrin-Binding to bacteria directly-Positive for soft tissue and bone infections-Uptake returns to normal after infection has cleared Several studies have suggested repeating gallium studies every 4 weeks -to assess treatment response -as reliable test to stop treatment if negative
  59. 59.  Indium scan:i. Type of white blood cell scintigraphyii. More reliable than CT in detectioniii. Can be used to monitor response to treatmentiv. Further work needs to be performed on this modality to elucidate its role in skull base osteomyelitis
  61. 61. treatment Long process Meticulous aural toilet Antibiotic or antifungal agents: length of treatment dictated by patients clinical picture and inflammatory markers Hyperbaric oxygen:a. For cases of intracranial spreadb. When disease is recurrent or refractory to antibioticsc. Not enough data to provide recommendations
  62. 62. Role of surgery Central or atypical skull base osteomyelitis: diagnosis and treatment( Matthew P.A Skull Base 2009;19:247-254)a. Providing tissue that helps exclude a neoplastic pathologyb. Allowing reliable culture of microorganism responsible
  63. 63. Anti pseudomonal antibiotics Aminoglycosides: gentamicin , amikacin, tobramycin Quinolones: ciprofloxacin, levofloxacin Cephalosporin: ceftazidim, cefepime, cefoperazone, cefpirome, ceftobiprole Antipseudomonal penicillins:i. Carboxypenicillins: carbenicillin, ticarcillinii. Ureidopenicillins: piperacillin, azlocillin, mezlocilliniii. Carbapenems: meropenem, imipenem, doripenemiv. Polymyxins: plymyxinB, colistinv. Monobactams: aztreonamRoute : all I.V exceptOral : fluroquinolonesAerosolized: tobramycin, aztreonam
  64. 64. Role of surgery Malignant otitis externa with skull base osteomyelitis(E. Illing JSCR.2011;5:6)a. Surgical resection of diseased bone not recommended due to disease spread through fascial and vascular planesb. Biopsies can be obtainedc. Any abscess can drainedd. In the presence of facial nerve palsy, decompression is not indicated
  65. 65. Final Conclusion Cranial nerve palsies in elderly diabetic or immunocompromised patient imaging finding of a lesion causing bony destruction in skull base should raise concern of a diagnosis of SBO Past history of otitis externa even if resolved before onset of presenting symptoms should raise suspicion of an underlying infective cause Prompt diagnosis with nuclear and CT imaging, biopsy to rule out malignancy and culture (aerobic, anaerobic, and fungal) is essential High dose oral quinolones can be started in established pseudomonal infection Early diagnostic sampling recommended in patients at increased risk of fungal SBO to enable optimal antimicrobial and surgical management The length of time of therapy continued guided by clinical findings, normalization of inflammatory markers, resolution on MRI, gallium scan findings Intracranial extension and multiple cranial nerves can be correlated with mortality
  66. 66. Monitoring progress in infectionClinical features in monitoring Severe otalgia, exudates, granulationsSerial inflammatory markers CRP, ESRMonitoring glycaemic control Capillary blood glucoseMonitoring imaging Gallium citrate scan/SPECT MRI CTComplications Facial +/- other cranial neuropathy, dural sinus thrombosis, meningitis, cerebral abscess, other